1) One-time gene gun or intramuscular (i.m.) rabies DNA vaccination protects non-human primates against rabies virus challenge > one year after vaccination. 2)Neutralizing antibody is detected at least 50 days earlier in gene gun as compared to i.m. vaccinated monkeys. There is no correlation between the concentration of DNA used for vaccination, the neutralizing antibody responses elicited and protection against viral challenge. To our knowledge, this is the first study to demonstrate long-term protection against a human viral pathogen using a DNA vaccination protocol that does not include a booster immunization 3)Mice vaccinated at 2 different intervals intradermally (i.d.) in the ear pinna and via gene gun over the axillary and inguinal lymph nodes with a rabies DNA vaccine produce neutralizing antibody 5 days after the primary vaccination. 4) Post-exposure rabies DNA vaccination, in combination with a non-protective dose of anti-rabies immune serum, protects mice against rabies virus. Thus, post-exposure therapy, substituting a DNA vaccine for the commercial human diploid cell vaccine, does not compromise protection against rabies virus. This study is the first, to our knowledge, to demonstrate post-exposure protection against a viral infection with a DNA vaccine. 5)Dogs vaccinated i.d. in the ear pinna with a rabies DNA vaccine produce superior neutralizing antibody responses as compared to dogs vaccinated i.m., via gene gun, or i.d. in the neck with the same vaccine. 6) Mice passively administered sera from dogs vaccinated with a rabies DNA vaccine are protected against rabies virus challenge. 7) Transcutaneous immunization with a rabies DNA vaccine protects mice against rabies virus. 8) Cattle immunized i.d. with a rabies DNA vaccine in the caudal tail-fold and the ear pinna produce higher titers of neutralizing antibody than cattle vaccinated in one site only. 9) Post-exposure treatment with the broad-spectrum anti-viral drug ribavirin (virazole) protects mice against rabies virus.